Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells

Gene Ther. 2006 Dec;13(24):1714-23. doi: 10.1038/sj.gt.3302808. Epub 2006 Jul 6.

Abstract

Antigen-presenting cells such as dendritic cells (DCs) play a critical role in inducing and regulating immune responses. One effective strategy for DC-based immunotherapy is to regulate maturation and function of DC. In this study, we apply single-walled carbon nanotubes (SWNTs) to carry small interfering RNA (siRNA) to reach, enter and genetically modify DCs in vivo. We prepared positively charged SWNTs (SWNTs+) using 1,6-diaminohexane which was demonstrated by transmission electron microscopy equipped with energy-dispersive X-ray spectroscopy and atomic force microscope. The functionalized SWNTs+ could absorb siRNA to form complexes of siRNA with SWNTs. These siRNA:SWNT+ complexes were preferentially taken up by splenic CD11c+ DCs, CD11b+ cells and also Gr-1+CD11b+ cells comprising DCs, macrophages and other myeloid cells to silence the targeting gene. Suppressor of cytokine signaling 1 (SOCS1) restricts the ability of DCs to break self-tolerance and induce antitumor immunity. Infusion of SWNTs+ carrying SOCS1siRNA reduced SOCS1 expression and retarded the growth of established B16 tumor in mice, indicating the possibility of in vivo immunotherapeutics using SWNTs-based siRNA transfer system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Antigen-Presenting Cells / physiology*
  • B7-1 Antigen / analysis
  • B7-1 Antigen / genetics
  • Blotting, Western / methods
  • Flow Cytometry
  • Gene Expression
  • Genetic Therapy / methods*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Nanotubes, Carbon
  • Neoplasm Transplantation
  • Phagocytosis
  • RNA Interference*
  • RNA, Small Interfering / administration & dosage*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / analysis
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Transfection / methods

Substances

  • B7-1 Antigen
  • Nanotubes, Carbon
  • RNA, Small Interfering
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins